PROJECT SUMMARY/ABSTRACT We are applying for matching funding to purchase a second Illumina NovaSeq 6000 sequencing system to handle increased sequencing needs from NIH-funded projects at the University of California at San Francisco (UCSF). Our current NovaSeq is approaching capacity and we will not be able to accommodate projects that are ramping up. The NovaSeq will be placed in the UCSF Center for Advanced Technology (CAT) core facility. The CAT is the only high throughput core facility at UCSF dedicated on research projects. The CAT was founded almost 20 years ago and has had a rich history of providing access and services to genomics technologies, starting with microarrays and transitioning to next-generation sequencing (NGS) over a decade ago starting with the original Solexa 1G sequencer to the Illumina NovaSeq. At UCSF, 36 labs in 21 departments have utilized the NovaSeq. We have also provided support for labs and core facilities at sister UC campuses such as UC Berkeley, UC Davis, UC Irvine, UC Riverside, and UC San Diego. The projects and applications span the gamut and include cancer genomics and epigenomics, metagenomic sequencing, functional genomics, single cell sequencing, massively parallel reporter assays, autoimmunity, and HIV/ADIS work. UCSF researchers have been pioneers in the development and deployment of genomic methods such as ribosome profiling, CRISPRa/i screens, and many types of single-cell sequencing methods. The CAT and its sequencing services have been integral to this work. Besides running the sequencing systems, the highly trained CAT staff provides deep domain knowledge that accelerates the progress of science and projects at UCSF and beyond.